Differential expression of TGFβ isoforms by human articular chondrocytes in response to growth factors

✍ Scribed by Peter M. Villiger; Martin Lotz

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 883 KB
• Volume: 151
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041510213

✦ Synopsis

Transforming growth factor P (TGFP) is a family of important regulators of chondrocyte growth and differentiation. Although TGFP has been detected in cartilage, the TGFj3 isoform5 expressed by chondrocytes and their regulation by growth factors are unknown. This study shows that human articular chondrocytes release TGFP activity. Chondrocyte conditioned media contains active TGFP and larger quantities in latent form. By neutralization with specific antibodies it is shown that all three isoforms (TGFP1, TGFP2, and TGFP3) are secreted by chondrocytes.

Analysis of the inducers of TLFP gene expression demonstrates complcx regulation of TGFP production by growth factors. Basic fibroblast growth factor (bFGF) stimulates the release of TGFp activity but has no effect on steady state TGFP mRNA levels while platelet-derived growth factor (PDGF) upregulates TGFPl and TGFP3 mRNAs with a corresponding increase in protein secretion. The three TGFP isoforms themselve5 differentially affect gene expression. While TGFPl and TGFP2 show autoinduction, TGFP3 upregulates TGFPl but does not affect TGFP2 mRNA levels.

These results demonstrate that human articular chondrocytes produce all three TCFP isoforms. Induction of TCFP expression is differentially regulated by various growth factors and occurs at the mKNA level and/or posttranscriptionally. Chondrocyte expression and the differential regulation of TGFP1, TGFPZ, and TGFP3 by growth factors suggest that all three isoforms of TGFP are part of the network of cartilage regulatory factors. Q 1992 Wiley-Liss. Inc.